TGF-8027
TGF-8027, or TGF-8-027, also known as N--2,5-dimethoxy-4-cyanophenethylamine, is a highly selective serotonin 5-HT2A receptor agonist and putative serotonergic psychedelic of the phenethylamine, 2C, and 25-NB families. It is one of the most selective serotonin 5-HT2A receptor agonists known and shows much greater selectivity than earlier agents like 25CN-NBOH, DMBMPP, and LPH-5. The drug produces psychedelic-like effects in rodents and hence may be hallucinogenic in humans. TGF-8027 was first described in the literature in 2025.
Pharmacology
Pharmacodynamics
TGF-8027 acts as a highly selective serotonin 5-HT2A receptor full agonist. Its affinities were 7.4nM at the serotonin 5-HT2A receptor, 390nM at the serotonin 5-HT2B receptor, and 1,100nM at the serotonin 5-HT2C receptor. The drug's and values in terms of Gq dissociation were 3.3nM at the human serotonin 5-HT2A receptor, 7,600nM at the human serotonin 5-HT2B receptor, and 160nM at the human serotonin 5-HT2C receptor. It was also assessed at these receptors with other assays. In addition, TGF-8027 was screened at a large panel of other targets, including receptors and transporters, and showed relatively little affinity at these sites.With regard to selectivity for the human serotonin 5-HT2A receptor over the human serotonin 5-HT2C receptor, TGF-8027 showed 149-fold selectivity in terms of affinity, 48.5-fold selectivity in terms of Gq dissociation, 84.5-fold selectivity in terms of calcium flux, and 2,450-fold selectivity in terms of IP1 accumulation. It is far more selective as an agonist of the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor than previous selective serotonin 5-HT2A receptor agonists such as 25CN-NBOH, DMBMPP, and rac-LPH-5. Previous research had not rigorously assessed the selectivity of these earlier compounds via employment of multiple selectivity assays.
TGF-8027 was less selective for the mouse serotonin 5-HT2A receptor over the mouse serotonin 5-HT2C receptor, but still showed about 15-fold selectivity for the former over the latter in terms of Gq dissociation. In accordance with its serotonin 5-HT2A receptor activation, the drug robustly induces the head-twitch response, a behavioral proxy of psychedelic effects, in mice. As such, it would be expected to produce psychedelic effects in humans.
The compound is a racemic mixture of - and -enantiomers, with the -enantiomer being a more potent serotonin 5-HT2A receptor agonist but the -enantiomer being more selective for activation of the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor.